A Novel Oxidative Phosphorylation-Associated Gene Signature for Prognosis Prediction in Patients with Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a common type of malignant tumor with high morbidity and mortality. The oxidative phosphorylation (OXPHOS) metabolic pathway produces adenosine triphosphate (ATP) by delivering electrons to transmembrane protein complexes in the mitochondria. This research was dedicated to identifying an OXPHOS-associated signature for the assessment of prognosis of HCC patients. A total of 371 HCC patients from the Cancer Genome Atlas (TCGA) and 231 HCC patients from the International Cancer Genome Consortium (ICGC) with RNA expression data and clinical data were employed as construction and validation cohorts, respectively. The least absolute shrinkage and selection operator (LASSO) Cox regression was applied to establish a multigene signature in the TCGA cohort, and the ICGC cohort was used for validation. The prognostic value of the risk signature was evaluated using univariate and multivariate Cox regression, Kaplan–Meier curves, and receiver operating characteristic (ROC) curves. The potential enrichment of biological functions was investigated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Meanwhile, we analyzed the correlation between the risk score and the tumor microenvironment (TME). A five-gene signature including ATP6V0B, ATP6V1C1, ATP6V1E1, TIMM9, and UQCRH was identified by LASSO Cox regression to classify patients into low- and high-risk groups. ROC curve analysis indicated that the five-gene signature is a prospective prognostic factor in HCC patients. Univariate and multivariate Cox regression analyses demonstrated that the risk score was an independent prognostic factor for overall survival (OS). Functional analysis showed that differentially expressed genes (DEGs) between the low- and high-risk groups were enriched in mitosis and the cell cycle pathway. In addition, the five-gene signature was associated with innate immune cell infiltration, immune subtypes, and tumor stemness. A novel OXPHOS-associated gene signature can be used for prognostic prediction for patients with HCC.